tetano
Editor, Senior Moderator
Bioorg Med Chem Lett
. 2024 Nov 1:130014.
doi: 10.1016/j.bmcl.2024.130014. Online ahead of print. Structural basis of the C-terminal domain of SARS-CoV-2 N protein in complex with GMP reveals critical residues for RNA interaction
Xincheng Ni[SUP] 1 [/SUP], Yinze Han[SUP] 1 [/SUP], Jiao Yu[SUP] 1 [/SUP], Renjie Zhou[SUP] 1 [/SUP], Jian Lei[SUP] 2 [/SUP]
Affiliations
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein performs multiple functions during the viral life cycle, particularly in binding to the viral genomic RNA to form a helical ribonucleoprotein complex. Here, we present that the C-terminal domain of SARS-CoV-2 N protein (N-CTD) specifically interacts with polyguanlylic acid (poly(G)). The crystal structure of the N-CTD in complex with 5'-guanlylic acid (GMP, also known as guanosine monophosphate) was determined at a resolution of approximately 2.0 Å. A novel GMP-binding pocket in the N-CTD was illustrated. Residues Arg259 and Lys338 were identified to play key roles in binding to GMP through mutational analysis. These two residues are absolutely conserved in the other two highly pathogenic CoVs, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Overall, our findings expand the structural information on N protein interacting with guanylate and reveal a conserved GMP-binding pocket as a potential antiviral target.
Keywords: Crystal structure; Guanylate; Nucleocapsid protein; RNA binding; SARS-CoV-2.
. 2024 Nov 1:130014.
doi: 10.1016/j.bmcl.2024.130014. Online ahead of print. Structural basis of the C-terminal domain of SARS-CoV-2 N protein in complex with GMP reveals critical residues for RNA interaction
Xincheng Ni[SUP] 1 [/SUP], Yinze Han[SUP] 1 [/SUP], Jiao Yu[SUP] 1 [/SUP], Renjie Zhou[SUP] 1 [/SUP], Jian Lei[SUP] 2 [/SUP]
Affiliations
- PMID: 39489230
- DOI: 10.1016/j.bmcl.2024.130014
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein performs multiple functions during the viral life cycle, particularly in binding to the viral genomic RNA to form a helical ribonucleoprotein complex. Here, we present that the C-terminal domain of SARS-CoV-2 N protein (N-CTD) specifically interacts with polyguanlylic acid (poly(G)). The crystal structure of the N-CTD in complex with 5'-guanlylic acid (GMP, also known as guanosine monophosphate) was determined at a resolution of approximately 2.0 Å. A novel GMP-binding pocket in the N-CTD was illustrated. Residues Arg259 and Lys338 were identified to play key roles in binding to GMP through mutational analysis. These two residues are absolutely conserved in the other two highly pathogenic CoVs, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Overall, our findings expand the structural information on N protein interacting with guanylate and reveal a conserved GMP-binding pocket as a potential antiviral target.
Keywords: Crystal structure; Guanylate; Nucleocapsid protein; RNA binding; SARS-CoV-2.